Description: This is the first submission for continued funding of the neuropathology section which aims to test the hypothesis that a specific dysregulation of the GABA-ergic system in tandem with alterations in dopaminergic innervation of cortical pyramidal and non-pyramidal neurons. In the past few years, the principal investigator has amassed a considerable body of evidence which supports the hypothesis that the GABAergic system is altered in schizophrenia. Additionally, over the past granting period the principal investigator was able to develop techniques to localize D1 and D2 receptors, measure glutamate neuron fiber diameters, and to suggest that GAD-IR terminals in the anterior cingulate cortex are altered in schizophrenia. The principal investigator has also found that TH-IR varicosities are similarly altered in schizophrenia and demonstrated a high degree of correlation between the two measurements. These are novel and interesting findings. The neuropathology section of this program project application is designed to continue Dr. Benes' ongoing and highly regarded work examining the neurochemical anatomy of the GABA and catecholamine systems in the anterior cingulate cortex of postmortem brain samples. This work would replicate, and in some areas extend, an extensive body of earlier work, utilizing immunocytochemical and high-resolution receptor autoradiography techniques. A particularly promising component of this planned work is to not only study the neurochemical anatomy of the anterior cingulate in schizophrenics and controls, but to include groups of subjects with bipolar disorder, first-degree relatives of both schizophrenics and bipolar patients, as well as a series of normal, non-psychiatrically ill teenagers. This approach should help to resolve if the changes (noted in the past from this laboratory) are associated with genetic factors and/or related to possible abnormal developmental processes.